Insulin is a well-known anabolic hormone. The mechanism of insulin's protein anabolic effect remains controversial. Although insulin undoubtedly inhibits protein degradation, its effect on protein synthesis is incompletely defined. Recent studies reviewed in this article highlight the methodologic limitations in studying the effect of insulin on protein synthesis. These methodological issues are related to the hypoaminoacidemia that ensues after insulin administration and to the difficulty in measuring the obligatory precursor pool (aminoacyl tRNA) label. Differential responses to unweighing in different muscle proteins has been demonstrated. The protein loss during unweighing is due to the loss of myofibrillar proteins, although sarcoplasmic proteins are spared. A recent study has found that lipid emulsion has no effect on whole protein degradation but decreases forearm protein degradation and synthesis. Age-related muscle wasting in humans has been shown to be related to a decline in fractional myofibrillar protein synthesis rate. Although some progress has been made by recent studies, refined methodologies are needed to define the regulation of muscle protein turnover in humans.